1. Field of the Invention
The present invention relates generally to a drug delivery apparatus for selectively and locally delivering a drug to internal body tissue. More specifically, the present invention relates to an apparatus for providing electric current/voltage in conjunction with a catheter to selectively and locally deliver a drug to internal body tissue, wherein the electric current/voltage is controlled in synchronization with active pacing of cardiac electrical activity.
2. Description of the Related Art
Many techniques exist for delivering drugs or other medicaments to body tissue. These include, among others; oral administration; injection directly into body tissue such as through an intramuscular injection or the like; topical or transcutaneous administration where the drug is passively absorbed, or caused to pass, into or across the skin or other surface tissue; and intravenous administration which involves introducing a selected drug directly into the blood stream.
The advantages of localized internal drug delivery over systemic administration are known and described in, for example, commonly assigned U.S. patent application Ser. No. 07/937,464 filed Aug. 28, 1992 now U.S. Pat. No. 5,286,254, which is hereby incorporated by reference. That application also discusses some situations in which localized internal drug delivery is especially advantageous, including the treatment of a dilated vessel to reduce restenosis following PTCA (Percutaneous Transluminal Coronary Angioplasty) and the delivery of drugs to tumors.
U.S. patent application Ser. No. 07/937,464 filed Aug. 28,1992 now U.S. Pat. No. 5,286,254 also discusses the use of iontophoresis to enhance localized internal drug delivery. Problems are, however, associated with introducing an electrical current into the body, including muscle stimulation and contraction, as well as pain or other unwanted sensations. More importantly, the problem of cardiac arrhythmia (irregular rhythm) can easily arise when electrical current passes through the heart. The current source causing that problem can originate from an external source, within the heart itself, or adjacent to the heart--such as from a coronary artery.
Intensity (current density), frequency, waveform and duration of the electrical current used in iontophoresis have an effect on whether cardiac arrhythmias and other problems will occur, as well as the magnitude of those reactions. The threshold at which ventricular fibrillation occurs with various transthoracic and intracardiac electrical levels increases with higher frequency currents. The threshold of sensation also increases with higher frequencies.
One attempt to minimize the risk of iontophoresis-induced arrhythmias is disclosed in U.S. Pat. No. 5,087,243. An implanted myocardial iontophoresis patch system is disclosed there in which a pulsed current is supplied to the anodal patch. Electrical activity in the patient's heart is monitored and the iontophoresis current is pulsed on and off in synchronization with ventricular depolarization to avoid the interval during which the heart is vulnerable to electrically induced arrhythmias or unnatural heart rhythms.
This system suffers from the inherent inaccuracies of passive monitoring of cardiac electrical activity. Those inaccuracies can cause the delivery of iontophoretic electric current at the wrong time during a cardiac cycle which could cause cardiac arrhythmias.
Also, passive monitoring alone may not prevent arrhythmias if higher iontophoretic currents are used (e.g., greater than 1 mA/cm.sup.2). Also, the disclosed preferred 80-100 msec pulses will not prevent vascular muscle stimulation resulting in vaso-constriction and may cause other unwanted stimulation or sensations.
Furthermore, the system described in U.S. Pat. No. 5,087,243 does not represent an optimized method for non-implantable iontophoretic drug delivery systems used near the heart. Non-implantable systems using catheters and other temporary devices preferably minimize the time of administration. An implantable system such as that described in U.S. Pat. No. 5,087,243 is, however, not optimized to minimize the time of administration as the system is always in place. By providing current for iontophoresis only during ventricular depolarization, the system of U.S. Pat. No. 5,087,243 cannot actively deliver any drug during a large percentage of the available time.
U.S. Pat. No. 5,236,413 to Feiring also discloses on/off pulsing of iontophoretic current in synchronization with passively monitored cardiac electrical activity to reduce the risk of inducing arrhythmias while enhancing drug delivery iontophoretically. As with the implantable system described above, however, the effectiveness of drug delivery is again limited by the relatively high proportion of time during which iontophoretic current is not provided.
Another disadvantage of the Feiring device and method is reliance on passive monitoring of cardiac electrical activity to minimize the risk of arrhythmias. Passive monitoring is not always accurate and the chance exists for errors which could result in cardiac arrhythmias.
Accordingly, there is a need in the art for an apparatus for delivering a drug selectively and locally to internal body tissue with a catheter using electric current/voltage controlled in conjunction with active pacing of cardiac electric activity.